Clinical Review


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Key findings and guidance from the past year on hot flushes, early menopause, and the hormone therapy–venous thromboembolism link. Plus, NAMS updates its position on estrogen-only and estrogen–progestin HT.



Important developments in the care of menopausal women in the past 12 months include:

  • new evidence about the duration, and nonhormonal management, of hot flushes
  • new data on the risk of venous thromboembolism when oral and transdermal hormone therapy (HT) are compared
  • trends in thinking regarding ovarian conservation at the time of hysterectomy, as well as a new report on the impact of hysterectomy on subsequent ovarian function
  • a new Position Statement on HT from the North American Menopause Society.

Hot flushes can last 10 years or longer

Freeman EW, Sammel MD, Lin H, Liu Z, Gracia CR. Duration of menopausal hot flushes and associated risk factors. Obstet Gynecol. 2011;117(5):1095–1104.

Levis S, Strickman-Stein N, Ganjei-Azar P, Xu P, Doerge DR, Krischer J. Soy isoflavones in the prevention of menopausal bone loss and menopausal symptoms: A randomized, double-blind trial. Arch Intern Med. 2011;171(15):1363–1369.

Hot flushes are more persistent than has been recognized

Previous reports have suggested that hot flushes, the most prevalent menopausal symptom, persist from 6 months to longer than 5 years. Freeman and colleagues carried out a prospective, population-based study in the Northeastern United States that enrolled more than 250 women (age range at enrollment, 35 to 47 years) who did not use HT. Subjects in this cohort were followed for 13 years as they progressed through menopause.

Surprisingly, the researchers found that the median duration of moderate-to-severe hot flushes was 10.2 years. Hot flushes persisted longer in black women than in white women (P = .02) and longer in non-obese women than in obese women (P = .003). Duration of symptoms was similar in smokers and nonsmokers.

Once again, soy fails to relieve menopausal symptoms

A number of clinical trials performed since the 2002 publication of the initial findings of the Women’s Health Initiative (WHI) have failed to demonstrate that soy is efficacious for treating menopausal symptoms. Nevertheless, many women remain intrigued by the potential for obtaining symptom relief with over-the-counter supplements.

Investigators in Florida randomized women who had been menopausal for at least 5 years to receive daily soy isoflavones (equivalent to about twice the amount ingested in a typical Asian diet) or placebo for 2 years. Outcomes assessed at baseline and again at 12 and at 24 months included spine and hip bone-mineral density (BMD), menopausal symptoms, and vaginal epithelial maturation. Almost 250 women (mean age, 52 years) were randomized.

At 2 years, researchers found that:

  • BMD had declined at all sites by about 2% in both groups
  • approximately one half of subjects in the soy group and approximately one third who were randomized to the placebo group reported experiencing hot flushes (P = .02)
  • vaginal epithelial maturation did not change appreciably from baseline in either group
  • constipation was reported by 31% of women in the soy group and 21% in the placebo group—a difference that only marginally achieved statistical significance.

Hormone therapy remains far and away the most effective treatment for vasomotor symptoms. The long-term prospective study of Freeman and colleagues clarifies that bothersome symptoms may persist for many years—an important (though not upbeat) counseling point for symptomatic women.

Highly effective nonhormonal treatment of vasomotor symptoms would represent a major advance for our menopausal patients. Regrettably, neither soy nor black cohosh1 offers relief greater than placebo.

Gabapentin and some serotonin reuptake inhibitor and serotonin–norepinephrine reuptake inhibitor antidepressants do offer a modestly more effective off-label treatment of hot flushes than does placebo,2 but their efficacy does not approach that of HT. In my practice, I find that many patients who suffer bothersome hot flushes are reluctant to try off-label use of antidepressants.

Hormone therapy and risk of venous thromboembolism

Laliberté F, Dea K, Duh MS, Kahler KH, Rolli M, Lefebvre P. Does the route of administration for estrogen hormone therapy impact the risk of venous thromboembolism? Estradiol transdermal system versus oral estrogen-only hormone therapy. Menopause. 2011;18(10):1052–1059.

Olié V, Plu-Bureau G, Conard J, Horellou MH, Canonico M, Scarabin PY. Hormone therapy and recurrence of venous thromboembolism among postmenopausal women. Menopause. 2011;18(5):488–493.

Transdermal HT appears to be safer than oral therapy

Yet another observational study adds evidence that venous thromboembolism (VTE) is less of a risk in women using transdermal estrogen therapy than it is in women taking oral therapy.

To compare oral and transdermal estrogen formulations in regard to the risk of VTE that they pose, Laliberte and colleagues conducted a retrospective cohort study of US and Canadian women, using health insurance claims data from women who were starting transdermal or oral estrogen. In all, 27,018 users of transdermal estrogen were matched with an equal number of oral users.


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